Patients with exertional chest pain are often found to have insignificant coronary artery disease or normal coronary arteries at coronary angiography. Coronary artery spasm of large epicardial vessels is frequently suggested as an etiology for angina in these patients, though standard challenges such as cold pressor testing and ergonovine infusion generally fail to provide angiographically demonstrable spasm. Twenty-two patients with chest pain and insignificant coronary artery disease underwent the same vasoconstrictor challenges along with rapid atrial pacing. Patients who experienced chest pain during the testing demonstrated biochemical evidence of myocardial ischemia, and coronary blood flow measurement revealed significantly less of an increase in coronary blood flow and less of a fall in coronary vascular resistance compared to patients who did not experience chest pain. No patient demonstrated large vessel coronary artery spasm. These studies suggest that coronary arterioles may have inadequate vasodilator reserve in some patients resulting in angina pectoris under certain conditions.